Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells

Hong, In Sun; Kim, Seok Hyun; Koong, Mi Kyoung; Jun, Jin Hyun; Kim, Sung Hoon; Lee, Yong Soon; Kang, Kyung Sun

doi:10.1093/humrep/deh424

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…The role of c-Jun in cellular proliferation, differentiation and apoptosis is well established [57], [58]. Studies also suggest that c-Jun can regulate neo intima formation and promote the proliferation and differentiation of vascular smooth muscle cells [59] and human endometrial cells [60]. AP-1 has been shown to be involved in the activation of matrix metalloproteinase (MMP) in progressive and unstable atherosclerotic plaques [61] as well as during the early disease process [52].…”

Section: Discussionmentioning

confidence: 99%

Network Analysis of Inflammatory Genes and Their Transcriptional Regulators in Coronary Artery Disease

et al. 2014

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Network analysis is a novel method to understand the complex pathogenesis of inflammation-driven atherosclerosis. Using this approach, we attempted to identify key inflammatory genes and their core transcriptional regulators in coronary artery disease (CAD). Initially, we obtained 124 candidate genes associated with inflammation and CAD using Polysearch and CADgene database for which protein-protein interaction network was generated using STRING 9.0 (Search Tool for the Retrieval of Interacting Genes) and visualized using Cytoscape v 2.8.3. Based on betweenness centrality (BC) and node degree as key topological parameters, we identified interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), interleukin-1 beta (IL-1B), tumor necrosis factor (TNF) and prostaglandin-endoperoxide synthase 2 (PTGS2) as hub nodes. The backbone network constructed with these five hub genes showed 111 nodes connected via 348 edges, with IL-6 having the largest degree and highest BC. Nuclear factor kappa B1 (NFKB1), signal transducer and activator of transcription 3 (STAT3) and JUN were identified as the three core transcription factors from the regulatory network derived using MatInspector. For the purpose of validation of the hub genes, 97 test networks were constructed, which revealed the accuracy of the backbone network to be 0.7763 while the frequency of the hub nodes remained largely unaltered. Pathway enrichment analysis with ClueGO, KEGG and REACTOME showed significant enrichment of six validated CAD pathways - smooth muscle cell proliferation, acute-phase response, calcidiol 1-monooxygenase activity, toll-like receptor signaling, NOD-like receptor signaling and adipocytokine signaling pathways. Experimental verification of the above findings in 64 cases and 64 controls showed increased expression of the five candidate genes and the three transcription factors in the cases relative to the controls (p<0.05). Thus, analysis of complex networks aid in the prioritization of genes and their transcriptional regulators in complex diseases.

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Section: Discussionmentioning

confidence: 99%

Network Analysis of Inflammatory Genes and Their Transcriptional Regulators in Coronary Artery Disease

et al. 2014

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“…showed, using immunohistochemistry, that c-jun expression occurs primarily in the proliferative phase of the menstrual cycle 80 , which was further supported by Hong et al . showing a correlation between growth in cultured endometrial stromal cells and activated c-jun expression 81 .…”

Section: Expression and Localization Of E2-erα C-fos C-jun And C-mmentioning

confidence: 94%

“…This finding suggests an important regulatory role for p38 in endometrial cell growth. Indeed, a modulatory role for p38 in human endometrial stromal cell differentiation and proliferation in the uterus has been reported 81 . Growth factors from uterine stromal cells regulate the uterine epithelia, and many of them (e.g., fibroblast growth factors-7 and -10, hepatocyte growth factor) signal via p38 MAPK 87 .…”

Section: Role Of P38 Mapk Signaling In Stromal Cell Differentiation Amentioning

confidence: 99%

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Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

2009

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The p38 mitogen-activated protein kinases (MAPKs) are members of discrete signal transduction pathways that have significant regulatory roles in a variety of biological processes, depending on the cell, tissue and organ type. p38 MAPKs are involved in inflammation, cell growth and differentiation and cell cycle. In the female reproductive system, p38 MAPKs are known to regulate various aspects of the reproductive process such as mammalian estrous and menstrual cycles as well as early pregnancy and parturition. p38 MAPKs have also been implicated in alterations and pathologies observed in the female reproductive system. Therefore, pharmacologic modulation of p38 MAPKs, and inter-connected signaling pathways (e.g., estrogen receptor signaling, c-fos, c-jun), may influence reproductive physiology and function. This article provides a critical, comparative review of available data on the roles of p38 MAPKs in the mammalian female reproductive system and in reproductive pathophysiology in humans and preclinical species. We first introduce fundamental differences and similarities of the mammalian female reproductive system that should be considered by toxicologists and toxicologic pathologists when assessing the effects of new pharmacologic agents on the female reproductive system. We then explore in detail the known roles for p38 MAPKs and related molecules in female reproduction. This foundation is then extended to pathological conditions in which p38 MAPKs are thought to play an integral role.

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“…Endometrial SCs that are persistent in the uterine endometrium from the fetal to the postmenopausal period [66] were found to differentiate into adipocytes, osteoblasts and chondrocytes as well [67,68] (Figure 4). The modulation of p38 and c-jun might play an important role for the differentiation and proliferation of normal human endometrial cells [69]. These differentiations can identify by positive staining, with Oil Red O (for lipid droplets), alizarin red (for osteogenesis), von Kossa (for calcified extracellular matrix), and Alcian blue (for sulfated proteoglycans), respectively.…”

Section: Introductionmentioning

confidence: 99%

Endometrial stem cells in regenerative medicine

et al. 2014

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First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

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Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells

Abstract: These results suggest that the modulation of p38 and c-jun may play an important role in the differentiation and proliferation of human endometrial cells.

Cited by 9 publications

References 28 publications

Network Analysis of Inflammatory Genes and Their Transcriptional Regulators in Coronary Artery Disease

Network Analysis of Inflammatory Genes and Their Transcriptional Regulators in Coronary Artery Disease

Species Comparison of the Role of p38 MAP Kinase in the Female Reproductive System

Endometrial stem cells in regenerative medicine

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